The Effect of Intracarotid Perfusion of Cerebrospinal Fluid from Patients with Subarachnoid Hemorrhage on Cerebrovascular Reactivity in Rats

Abstract

Cerebrovascular resistance was measured in 10 rats with increasing dosages of 5-Hydroxytryptamine (5-HT). The internal carotid artery was perfused at constant flow with cerebrospinal fluid (CSF) from patients with ruptured intracranial aneurysms, and dose-response curves to 10 μ 1 boluses of 5-HT were compared with similar dose-response curves obtained during perfusion with Krebs' solution and with nonnal CSF (CSF-N). CSF from patients with subarachnoid hemorrhage (CSF-SAH) produced increased sensitivity to 5-HT.     

Alaproclate a novel antidepressant?

Clinical and biochemical effects of two selective 5-HT uptake inhibitors, zimeldine and alaproclate, were studied in 24 hospitalized patients with endogenous depression. According to a randomized parallel group design 14 patients were treated with zimeldine and 10 with alaproclate. The dosage of both zimeldine and alaproclate was 200 mg daily. For the evaluation of the clinical effect, Montgomery & Asberg Depression Rating Scale (MADRS) was used. Seven of 14 patients treated with zimeldine and seven of 10 treated with alaproclate improved. 5-HT uptake inhibition in patients' platelets and concentration of amine metabolites (5-HIAA, HVA, HMPG) in CSF were studied before and during treatment. After 3 weeks of treatment with zimeldine 5-HIAA and HMPG in CSF decreased significantly while HVA in CSF increased significantly. Zimeldine produced a significant 5-HT uptake inhibition in platelets. During treatment with alaproclate no significant change in amine metabolites concentration in CSF was found and there were no mean changes on 5-HT uptake inhibition in platelets.     

Regulation of alpha-melanocyte-stimulating hormone release from superfused slices of rat hypothalamus by serotonin and the interaction of serotonin with the dopaminergic system inhibiting peptide release

Release of alpha-melanocyte-stimulating hormone (alpha-MSH) from frontal slices of rat hypothalamus superfused with oxygenated artificial cerebrospinal fluid (ACSF) was quantified by radioimmunoassay. Control depolarisations with 50 mM KCl-containing ACSF produced significant increases in alpha-MSH release which were partially blocked by 10(-6) M cinanserin, a serotonin (5-HT) receptor antagonist. Superfusion of the tissues with varying concentrations of 5-HT (10(-7) M to 10(-4) M) resulted in an inverted U-shaped dose-response curve, maximum alpha-MSH release being obtained with 10(-6) M 5-HT. Addition of 10(-6) M cinanserin shifted the 5-HT dose-response curve to the right whilst the presence of 10(-8) M flupenthixol, a dopamine receptor antagonist, resulted in a sigmoidal 5-HT dose-response curve. Superfusion with ACSF containing either 10(-7) M fluoxetine, a 5-HT re-uptake inhibitor, or 10(-7) M p-chloroamphetamine, an agent releasing 5-HT, induced significant increases in alpha-MSH release which were abolished in the presence of 10(-6) M cinanserin. These data demonstrate the presence of an endogenous 5-HT system that exerts a biphasic effect on alpha-MSH release. A stimulatory effect caused by lower 5-HT concentrations appears to be a direct action whilst an inhibitory effect at higher concentrations is mediated through an inhibitory endogenous dopaminergic system. A significant proportion of K+-stimulated peptide release is 5-HT-mediated.     

Effects of 21 days treatment with fluoxetine on stimulated endogenous 5-hydroxytryptamine overflow in the rat dorsal raphe and suprachiasmatic nucleus studies using fast cyclic voltammetry in vitro

Changes in the extracellular concentration of 5-HT evoked by electrical stimulation of brain slices containing either dorsal raphe nucleus (DRN) or suprachiasmatic nucleus (SCN) from rats treated for 21 days with fluoxetine (5 mg/kg; i.p.) or water were monitored using fast cyclic voltammetry (FCV). Stimulated 5-HT overflow was enhanced significantly in both brain regions after 21 days treatment with fluoxetine but there was no change in the half time for re-uptake (t1/2). Concentration response curves for inhibition of electrically stimulated 5-HT overflow by 8-OH-DPAT (5-HT_1a receptor agonist) or RU24969 (5-HT_1b receptor agonist) in the DRN or SCN respectively were obtained in slices prepared from both groups of animals. There was a significant shift to the right in the dose-response curve for RU24969 in the SCN in fluoxetine treated animals but a shift to the left for the dose-response curve for 8-OH-DPAT in the DRN. These data suggest that down regulation of the 5-HT_1b autoreceptors occurs in an axon terminal region (SCN) but that there is a sensitisation of 5-HT_1a autoreceptor mechanisms controlling 5-HT overflow in the DRN.     

Study of tryptophan metabolism via serotonin in cerebrospinal fluid of patients with noncommunicating hydrocephalus using a new endoscopic technique

By a recent minimally invasive neuroendoscopic technique, the cerebral ventricles have been reached in a quick, reliable, and harmless way, making possible the study of cerebrospinal fluid (CSF) of the lateral ventricles and, above all, the CSF adjacent to the walls of the third ventricle. Tryptophan, 5-hydroxytryptophan, serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were measured in CSF by HPLC equipment. Twenty-six patients affected with noncommunicating hydrocephalus were enrolled in the study and, as controls, 28 subjects not suffering from any neurological disease. The concentrations of tryptophan were higher in right ventricular CSF than in lumbar CSF (P < 0.01). 5-HT was detectable in the CSF of the right ventricle of hydrocephalic patients. 5-HIAA was higher in right ventricular CSF than in cisternal and lumbar CSF (P < 0.01), both in controls and in hydrocephalic patients. However, there was a higher concentration of 5-HIAA in right ventricular (P < 0.05) and cisternal (P < 0.01) CSF in hydrocephalic patients in comparison with controls. In the CSF samples withdrawn during neuroendoscopy, 5-HT presented the highest concentrations in the pineal recess. The highest amounts of 5-HIAA were found in the choroid plexus, third and right ventricles, pituitary recess, and aqueduct, and the lowest in pineal recess, subarachnoid space, infundibulum, and interpeduncolar cistern. These results provide new insight into the fate of tryptophan and its metabolites via serotonin in the CSF and suggest the feasibility of the new neuroendoscopic technique for brain metabolic studies.     

蛛网膜下腔出血后迟发性脑血管痉挛与五羟色胺的关系

通过荧光分光方法测定了蛛网膜下腔出血(SAH)后迟发性脑血管痉挛(DCVS)时的病人及实验动物血清与脑脊液(CSF)中5—HT的含量。实验结果显示DCVS时病人及实验动物CSF中5—HT的含量处于很低水平,并且实验动物CSF中5—HT的含量在SAH后的第七天比出血后的第三天还要低。DCVS病人血清中5—HT含量也较正常对照组明显降低。本研究结果提示5—HT与DCVS的发生无明显关系。     

Serotoninergic system in dementia of the Alzheimer type. Abnormal forms of 5-hydroxytryptophan and serotonin in cerebrospinal fluid

Serotonin (5-HT), its precursor 5-hydroxytryptophan (5-HTP), and its major metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured in the cerebrospinal fluid (CSF) of 14 patients with dementia of the Alzheimer type (DAT) and in nine controls by high-performance liquid chromatography with a novel multisensor coulometric detection system. Concentrations of both 5-HT and 5-HIAA detected by this system were lower than the concentrations obtained using conventional amperometric detection. This difference was caused by coelution of compounds that could be resolved from 5-HT and 5-HIAA by the multisensor coulometric system. One of the coelution compounds, observed in DAT but not in control CSF, behaved like a partially oxidized 5-HT. A compound behaving like partially oxidized 5-HTP was also observed in DAT CSF. Concentrations of 5-HTP, 5-HT, and 5-HIAA were lower in DAT CSF than in a corresponding fraction of control CSF. These results indicate involvement of the serotoninergic system in DAT and might lead to development of a diagnostic test for DAT.     

Changes in CSF tryptophan metabolite levels in infantile spasms]

Cerebrospinal fluid (CSF) from 6 cases of asymptomatic infantile spasms (IS) (mean age, 6.1 months) was collected before and after treatment with adrenocorticotropic hormone (ACTH). The concentration of CSF tryptophan (TRP) metabolites was analyzed using HPLC and compared to the metabolite concentration in CSF from 10 age-matched controls (mean age, 6.7 months). Levels of CSF serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and kynurenine (KYN) at pretreatment were significantly lower in IS patients compared to controls (p < 0.05). In contrast, the levels of CSF 3-hydroxykynurenine (3-OHKY) before ACTH treatment were significantly higher in IS patients than in controls (p < 0.05). After the treatment, significant increases in 5-HIAA and decreases in KYN and 3-OHKY levels (p < 0.05) were observed in CSF of infants whose seizures were eliminated by ACTH. These findings suggested that the presence of seizures in IS was associated with a significant decrease in serotonergic activity, or that the turnover in the direction of 3-OHKY was altered. The possibility that elimination of seizures by ACTH might be related to decreased production of kynurenine metabolites was discussed.     

Indole levels in human lumbar and ventricular cerebrospinal fluid and the effect of L-tryptophan administration

Levels of tryptophan (TRP), 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in human lumbar and ventricular cerebrospinal fluid (CSF) were measured by reversed phase liquid chromatography (HPLC) with electrochemical detection. The levels of TRP ranged from 1593 to 4865 nmol/l in ventricular (VF) and from 1257 to 2557 nmol/l in lumbar CSF. The level of 5-HTP varied from 1.1 to 68.9 nmol/l in VF and from 5.3 to 10.8 nmol/l in lumbar CSF; no previous reports of 5-HTP levels in CSF exist. The serotonin level was 1.9-27.3 nmol/l in VF and 5.7-12.0 nmol/l in lumbar CSF. The levels of 5-HIAA were considerably higher in VF than in lumbar fluid with respective means of 498 +/- 52.4 nmol/l and 112 +/- 15.6 nmol/l (P less than 0.001). An oral dose of 2 g L-tryptophan significantly increased all indole levels except that of 5-HT, both in patients with progressive myoclonus epilepsy and in controls.     

Serotonin and 5-hydroxyindoleacetic acid in CSF. Difference in Parkinson's disease and dementia of the Alzheimer's type

Serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured in the sixth, 13th, and 20th milliliters of CSF in patients with dementia of the Alzheimer's type (DAT) and Parkinson's disease (PD), and in an aliquot of CSF in controls. In patients with PD there was a positive correlation between 5-HT and 5-HIAA levels in the 20th milliliter of CSF, while in patients with DAT there was a negative correlation of these levels in this CSF fraction. In patients with the senile form of DAT the 5-HIAA levels in the 20th milliliter of CSF were higher than in patients with PD. These results indicate differential involvement of the serotoninergic system in DAT and PD, and may lead to the development of a chemical marker for DAT.     

Effects of citalopram, a synthetic serotonin uptake inhibitor, on indoleamine and catecholamine concentrations in the cerebrospinal fluid of freely moving rats

Summary We studied changes in the concentrations of 5-hydroxytryptamine (5-HT), other indoleamines, and catecholamines in the cerebrospinal fluid (CSF) of freely-moving rats that had been administered citalopram, ±1-[3-(Dimethylamino)propyl)-1-(4-fluorophenyl)-1, 3-dihydro-5-isobenzofurancarbonitrile hydrobromide), a selective inhibitor of 5-HT uptake. In a microdialysis experiment, the intracerebral extracellular free 5-HT increased significantly, peaking 60 to 90 min after citalopram (30 mg/kg p.o.) was administerd. The 5-HT concentrations in CSF from the cisterna magna increased significantly, reaching a maximum 6 hours after a single dose of citalopram (30 mg/kg p.o.) was given. Six hours after this dose, the CSF 5-HT concentration in the cisterna magna was significantly increased, and the 5-hydroxyindoleacetic acid (5-HIAA) concentration was significantly decreased. There were non-significant changes in the other indoleamines (tryptophan, 5-hydroxytryptophan, and kynurenine) and in the catecholamines (dopamine, homovanillic acid, normetanephrine, and 3-methoxy-4-hydroxyphenethyleneglycol). The 5-HT/tryptophan ratio was correlated significantly with the kynurenine/tryptophan ratio before treatment with citalopram (r=0.81, p=0.051), indicative that there is coordination of the serotonin and kynurenine pathways in normal rats. In the animals posttreatment there was no such correlation, suggesting that the changes in 5-HT are independent of the kynurenine system at least within the 6 hours postreatment. These CSF results appear to reflect selective inhibition of 5-HT uptake in brain tissues by citalopram that is not associated with changes in catecholamines.     

Clinical, biochemical, and pharmacological observation in a patient with postasphyxic myoclonus: association to serotonin hyperactivity

Posthypoxic action myoclonus is usually associated with impaired serotonin (5-HT) neurotransmission but in some patients 5-HT precursors aggravate and 5-HT blockers improve action myoclonus. We studied a 65-year-old man who presented with action myoclonus following a prolonged episode of moderate hypoxia and severe hypercarbia. The myoclonus increased with 5-hydroxytryptophan (5-HTP) 1,200 mg/day plus carbidopa 300 mg/day and sodium salt of valproic acid (SVA) 800 mg/day, and improved with 1 mg of clonazepam (CNZ) in an intravenous bolus. Biochemical analysis of the cerebrospinal fluid (CSF) prior to any drug therapy did not reveal abnormalities in the levels of homovanillic acid (HVA) and methoxyhydroxyphenylglycol (MHPG) but 5-hydroxyindoleacetic acid (5-HIAA) levels were elevated in comparison with controls (33 versus 21 ng/ml). SVA therapy produced a moderate increase and 5-HTP plus carbidopa a threefold elevation of 5-HIAA in CSF and marked aggravation of action myoclonus. Methysergide (3 mg/day) totally suppressed myoclonus and decreased CSF 5-HIAA to undetectable levels. Methysergide also reduced CSF tryptophan to 40% of baseline levels. Discontinuation of methysergide and substitution by placebo was followed by reappearance of myoclonus. A partial and incomplete spontaneous remission of symptoms took place 7 months after the asphyxic episode. Action myoclonus and enhanced 5-HT neurotransmission may be present in patients in which acidosis reverses the effects of hypoxia on 5-HT neurotransmission.     

A double-blind study of zimelidine, a serotonin uptake inhibitor, and desipramine, a noradrenaline uptake inhibitor, in endogenous depression. II. Biochemical findings

In a comparative evaluation of zimelidine, a potent serotonin (5-HT) uptake inhibitor, and desipramine, a potent noradrenaline (NA) uptake inhibitor, 65 hospitalized patients with endogenous depression were evaluated for the following biochemical variables: 5-HT uptake in platelets, 5-HT concentration in whole blood, inhibition of the 5-HT and NA accumulation in rat hypothalamic synaptosomes incubated in the patients' plasma, the excretion of 4-hydroxy-3-methoxyphenyl glycol (HMPG) in urine and the pretreatment levels of the amine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and HMPG in cerebrospinal fluid (CSF). results of the biochemical studies confirmed that zimelidine and desipramine have different profiles with respect to monoamine uptake. Thus zimelidine caused more marked inhibition of 5-HT uptake than desipramine, especially in rat brain synaptosomes incubated in the patient's plasma. Desipramine plasma was much more effective than zimelidine plasma in inhibiting NA uptake in the same preparation. The urinary excretion of HMPG decreased significantly during desipramine treatment but remained unchanged during zimelidine treatment. The combined clinical and biochemical results indicated that patients with low pretreatment levels of 5-HIAA and HVA in CSF responded significantly better to zimelidine than patients with high levels of 5-HIAA and HVA. On the other hand, patients with high levels of 5-HIAA and HVA. On the other hand, patients with high levels of HMPG in CSF tended to respond better to desipramine than those with low levels of this NA metabolite.     

Relationship between DST and the serotonergic system. Results from treatments with two 5-HT reuptake blockers in dementia disorders

Dexamethasone suppression test (DST) were performed in patients with dementia of the Alzheimer type and multiinfarct dementia. Test–retest reliability was found to be high in dementia patients if they were inpatients and environmental factors were dept stable. In this group 14% were non-suppressors. If outpatients were investigated, admitted to hospital for only a few days, the test–retest reliability was low. In these patient groups 39–56% were non-suppressors. Treatment with the serotonergic (5-HT) uptake inhibitor citalopram significantly reduced the postdexamethasone cortisol levels as well at 08.00 am as at 03.00 pm the day after intake of 1 mg dexamethasone (after 10 h and 17 h respectively). Citalopram treatment also caused significant reduction of the cerebrospinal fluid (CSF) levels of 5-hydroxyindolacetic acid (5-HIAA) and 3-methoxy 4-hydroxyphenylglycol (HMPG). A correlation was seen between the citalopram-induced reduction of 5-HIAA levels in CSF and the degree of dexamethasone-induced suppression of cortisol concentrations after the treatment period. Treatment with the 5-HT uptake inhibitor alaproclate, with a regional selectivity principally to the limbic system, had little effect on the postdexamethasone cortisol levels. The results suggest a relation between the abnormal DST in dementia and a disturbed hypothalamic 5-HT function.     

抑郁症患者自杀与脑脊液单胺代谢产物的关系

目的：探讨抑郁症患者自杀与脑脊液单胺代谢产物之间的关系。方法：应用高效液相色谱法，测定24例抑郁症患者(自杀组10例，无自杀组14例)及25例对照组5-羟色胺(5-HT)代谢产物5-羟吲哚乙酸(5-HIAA)，去甲肾上腺素(NE)代谢产物3-甲基-4-羟苯乙二醇(MHPG)及多巴胺(DA)代谢产物高香草酸(HVA)的浓度。结果：抑郁症自杀组5-HIAA浓度显著低于对照组，男性自杀组5-HIAA浓度、HVA浓度和HVA／MHPG比值均显著低于男性对照组，女性则无显著差异：结论：抑郁症患者自杀可能与5-HT和DA功能低下以及DA和NE之间的关系改变有关。     

Cerebrospinal fluid 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in HIV-1 infection.

Reduced level of serotonin (5-hydroxytryptamine, 5-HT) in humans has been associated with a number of mental health and behavioral problems including depression, aggression, violence, sexual dysfunctions, sleep and eating disorders. Even though among HIV-1-infected individuals, prevalence of mental health and behavioral problems are common, their relationship with central nervous system serotonin functions is not clearly understood. This investigation was carried out to study the status of CSF 5-HT in HIV-1+ subjects (n = 21), in the early stage of infection, and HIV-1- control subjects (n = 24). Samples of CSF were obtained by lumbar puncture and were analyzed for 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), using high-performance liquid chromatography equipped with electrochemical detector. Levels of CSF 5-HT were significantly lower in the HIV-1+ group compared to the HIV-1- group. There was no significant difference in the CSF 5-HIAA levels between the two groups. In both groups, however, there was a significant correlation between CSF 5-HT and 5-HIAA. In the HIV-1 + group, although CSF 5-HT level was significantly negatively correlated with serostatus, there was no correlation between either CSF 5-HT or 5-HIAA levels and CD4 cell number or any behavioral measures evaluated in this study, including Beck's Depression Inventory and state/trait anxiety scores. These data suggest that HIV-1 infection affects the CNS 5-HT status with no significant association with measures of depression and anxiety, at least in the early stage of infection.     

Cerebral tryptophan metabolism in humans in relation to malignant pain

The authors investigated the cerebral metabolism of tryptophan in patients suffering from malignant pain by means of CSF dosage of tryptophan (Trp), 5-hydroxytryptophan (5-HTP), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA). The level of 5-HIAA in patients with pain was 66.48 +/- 13.67 ng/ml, while in those without pain was 25.05 +/- 13.25 ng/ml; the difference was statistically significant, p = 0.001. Trp, 5-HTP and 5-HT levels did not register significant differences in the two groups of patients, although a tendency to lower values was seen in patients with pain, supporting the hypothesis of increased turnover of this metabolic pathway in cancer patients. A statistically significant inverse correlation was also found between cerebral Trp levels and pain levels measured on the Scott-Huskisson visual analogue scale. The data obtained confirm the importance of the cerebral serotoninergic pathway in pain modulation and the interest which CSF analysis may have for the assessment of patients suffering from pain.     

Deficient serotonin neurotransmission and depression-like serotonin biomarker alterations in tryptophan hydroxylase 2 (Tph2) loss-of-function mice

Probably the foremost hypothesis of depression is the 5-hydroxytryptamine (5-HT, serotonin) deficiency hypothesis. Accordingly, anomalies in putative 5-HT biomarkers have repeatedly been reported in depression patients. However, whether such anomalies in fact reflect deficient central 5-HT neurotransmission remains unresolved. We employed a naturalistic model of 5-HT deficiency, the tryptophan hydroxylase 2 (Tph2) R439H knockin mouse, to address this question. We report that Tph2 knockin mice have reduced basal and stimulated levels of extracellular 5-HT (5-HT(Ext)). Interestingly, cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) and fenfluramine-induced plasma prolactin levels are markedly diminished in the Tph2 knockin mice. These data seemingly confirm that low CSF 5-HIAA and fenfluramine-induced plasma prolactin reflects chronic, endogenous central nervous system (CNS) 5-HT deficiency. Moreover, 5-HT(1A) receptor agonist-induced hypothermia is blunted and frontal cortex 5-HT(2A) receptors are increased in the Tph2 knockin mice. These data likewise parallel core findings in depression, but are usually attributed to anomalies in the respective receptors rather than resulting from CNS 5-HT deficiency. Further, 5-HT(2A) receptor function is enhanced in the Tph2 knockin mice. In contrast, 5-HT(1A) receptor levels and G-protein coupling is normal in Tph2 knockin mice, indicating that the blunted hypothermic response relates directly to the low 5-HT(Ext). Thus, we show that not only low CSF 5-HIAA and a blunted fenfluramine-induced prolactin response, but also blunted 5-HT(1A) agonist-induced hypothermia and increased 5-HT(2A) receptor levels are bona fide biomarkers of chronic, endogenous 5-HT deficiency. Potentially, some of these biomarkers could identify patients likely to have 5-HT deficiency. This could have clinical research utility or even guide pharmacotherapy.     

Regulation of α-melanocyte-stimulating hormone release from superfused slices of rat hypothalamus by serotonin and the interaction of serotonin with the dopaminergic system inhibiting peptide release

Release of α-melanocyte-stimulating hormone (α-MSH) from frontal slices of rat hypothalamus superfused with oxygenated artificial cerebrospinal fluid (ACSF) was quantified by radioimmunoassay. Control depolarisations with 50 mM KCl-containing ACSFm produced significant increases in α-MSH release which were partially blocked by 10⁻⁶ M cinnaserin, a serotonin (5-HT) receptor antagonist. Superfusion of the tissues with varying concentrations of 5-HT *10⁻⁷ M to 10⁻⁴ M) resulted in an inverted U-shaped dose-response curve, maximum α-MSH release being obtained with 10⁻⁶ M 5-HT. Addition of 10⁻⁶ M cinanserin shifted the 5-HT dose-response curve to the right whilst the presence of 10⁻⁸ M flupenthixol, a dopamine receptor antagonist, resulted in a sigmoidal 5-HT dose-response curve. Superfusion with ACSF containing either 10⁻⁷ M fluoxetine, a 5-HT re-uptake inhibitor, or 10⁻⁷ M p-chloroamphetamine, an agent releasing 5-HT, induced significant increases in α-MSH release which were abolished in the presence of 10⁻⁶ M cinanserin. These data demonstrate the presence of an endogenous 5-HT system that exerts a biphasic effect on α-MSH release. A stimulatory effect caused by lower 5-HT concentrations appears to be a direct action whilst an inhibitory effect at higher concentrations is mediated through an inhibitory endogenous dopaminergic system. A significant proportion of K⁺-stimulated peptide release is 5-HT-mediated.     

Indole amine deficiency in blood and cerebrospinal fluid from patients with human immunodeficiency virus infection

Twenty-four patients with human immunodeficiency virus (HIV) infection were investigated for possible changes in certain indole amine constituents in blood and cerebrospinal fluid (CSF). Albumin in serum was determined and used as a rough nutritional marker. Six of the 24 patients had acquired immunodeficiency syndrome AIDS, four had other clinical symptoms of HIV infection, and 14 had no apparent symptoms. The HIV-seropositive patients had significantly decreased tryptophan values; their blood concentrations were 28% lower and their CSF concentrations 30% lower than corresponding values in 14 healthy controls. The blood concentrations of 5-hydroxytryptamine (5-HT) were 50% lower, and the platelet content of 5-HT was 36% lower in HIV-infected individuals than in the control group. The most pronounced changes were invariably seen in the six cases with AIDS and in patients with a low number of CD4+ cells. No significant difference between controls and HIV-seropositive patients was detected in the mean CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA), although these levels were markedly reduced in four of the HIV patients. Neither was any significant difference seen between patients and controls in the serum concentrations of albumin.